1. Field of the Invention
The embodiments described herein are directed to methods and devices for the isolation and delivery of cells, such as lymphocytes, to patients, in particular patients undergoing a splenectomy. When administered to a patient, embodiments described herein may increase the patient's immunity and reduce the likelihood of a post-splenectomy infection.
2. Description of the Related Art
There are several medical conditions that often necessitate the removal of all or part of a patient's spleen, for example as a result of physical trauma, spontaneous rupture, malignancy, or enlargement secondary to conditions such as malaria, mononucleosis, or lymphoma. However, patients having undergone splenectomy procedures typically suffer from side effects including reduced immune function and a greater risk of overwhelming post-splenectomy infection (“OPSI”) due to sepsis from encapsulated microorganisms. This is a particular risk for patients whose spleens were removed during childhood.
As such, surgical treatment focuses on conserving the spleen if possible, especially when treating pediatric patients. If a splenectomy is required, an attempt may be made to preserve at least a portion of the spleen via a partial splenectomy. However, some cases still necessitate a complete splenectomy.
It can be rationalized that if the spleen serves as a filter to intravascular bacterial contaminants, a possible way of decreasing the risk of OPSI and other post-splenectomy complications would be to save the spleen or to autotransplant sections that can be salvaged. The structure of the spleen is thought to be an integral part involved in immune functionality. The vascular flow through the sinusoids allows antigenic debris to be presented to the resident reticuloendothelial cells lining the sinuses. These cells in turn can present processed antigen to activate other cells within the immune system. It has therefore long been felt that this ambiance of the spleen must be preserved in order to maintain function.
Accordingly, numerous studies have examined the feasibility of autologous splenic transplantation as a possible alternative in unsalvageable cases requiring splenectomy. Improved antibody responses along with increased levels of opsonins and tuftsin have been observed in some experimental models. Certain studies have shown that in order to achieve any benefit in humoral immunity, at least approximately half of the spleen should be retained. Some studies reported that good outcomes resulted from autotransplants within the mesentery in comparison to intramuscular transplants. Additionally, some studies have shown that improved antibody titers were obtained with intraperitoneal autotransplantation of splenic tissue. Further studies have shown an increased survival rate with a 50% splenectomy compared to a total splenectomy, in a mouse model, when exposed to a Streptococcal challenge.
However, splenic autotransplantation is not frequently practiced because of complications such as autotransplant fibrosis, aseptic necrosis, or bowel adhesion and/or obstruction. Such complications may necessitate further surgery. Additionally, there is some experimental evidence of a lack of efficacy of such autotransplants, as certain studies have shown that autotransplanted spleens have been found to undergo approximately 8% necrosis each year, and are therefore soon below optimal efficacy. Aside from function, it has also been noted that transplanted spleen sections have been found to have decreased size of peri-arteriolar lymphatic sheath (“PALS”) along with changes in density of B cell, macrophages and T-cell ratios. Not only have changes in parenchymal architecture been observed, but vasculature may also be altered by dilation of vessels in the marginal zone, pulp cords and red pulp where antigen presentation occurs in the spleen.
As stated above, the risks of OPSI are elevated in all splenectomized patients, and the most frequent causes of OPSI include encapsulated organisms, specifically Streptococcus pneumoniae. Currently, vaccine and antibiotic prophylaxis are used to help prevent OPSI in splenectomized patients. Although polyvalent pneumococcal vaccines are available and used for prophylaxis in cases of necessary splenectomy, there are cases where patients have still succumbed to fatal sepsis due to OPSI. Additionally, some studies have shown that serum titers against certain pneumococcal subtypes decline over time to nonprotective levels. Rather, although vaccination is most effective if given prior to splenectomy, this is not always possible.